Association Between the Phenotype and Genotype of Isoniazid Resistance Among Mycobacterium tuberculosis Isolates in Thailand
Received 13 December 2019
Accepted for publication 31 January 2020
Published 24 February 2020 Volume 2020:13 Pages 627—634
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Sahil Khanna
Ratchanu Charoenpak, 1 Wichai Santimaleeworagun, 2 Gompol Suwanpimolkul, 3–5 Weerawat Manosuthi, 6 Paweena Kongsanan, 6 Suthidee Petsong, 7 Chankit Puttilerpong 8
1College of Pharmacotherapy Thailand, Nonthaburi, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 3Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Tuberculosis Research Unit, Chulalongkorn University, Bangkok, Thailand; 5Emerging Infectious Diseases Clinical Center, Thai Red Cross, Bangkok, Thailand; 6Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand; 7Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 8Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
Correspondence: Chankit Puttilerpong
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok, Thailand
Tel|Fax +66 2 218 8403
Purpose: The emergence of isoniazid-resistant tuberculosis (HR-TB) is a global public health problem, causing treatment failure and high mortality rates. This study aimed to determine the minimal inhibitory concentration (MIC) of isoniazid and detect the gene mutation in HR-TB and any association between the level of isoniazid resistance and gene mutation.
Methods: We collected 74 clinical HR-TB isolates from two tertiary-care centers in Thailand. MICs were established using broth macrodilution. A line probe assay (LPA) was used to detect gene mutations that confer resistance to isoniazid, rifampicin, aminoglycosides, and fluoroquinolones.
Results: Sixty-one (82.4%) isolates were monoresistant to isoniazid and 44 (72.1%) were highly resistant to isoniazid. From the clinical isolates, the range of isoniazid MICs was 0.4– 16 μg/mL. The katG S315T gene mutation was the prominent mutation in both isoniazid-monoresistant TB (70.5%) and multidrug-resistant TB (72.7%) isolates. The positive predictive value (PPV) of katG was 100% in detecting high levels of isoniazid resistance. The PPV of the inhA mutation was 93.8% in detecting low levels of isoniazid resistance. Five isolates (6.8%) exhibited low-level phenotypic resistance, whereas an LPA failed to detect an isoniazid gene mutation. Our study found one HR-TB isolate with a gyrA fluoroquinolone-resistant gene mutation.
Conclusion: Most HR-TB isolates had high isoniazid-resistance levels associated with the katG gene mutation. High-dose isoniazid should be used with caution in patients with HR-TB. Early detection of drug resistance by genotypic assay can help determine an appropriate regimen.
Keywords: tuberculosis, isoniazid, minimal inhibitory concentration, line probe assay, gene mutation
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